This program represents a continuation and extension of closely coordinated clinical and basic laboratory efforts to: 1) further define the natural history, pathogenesis and pathophysiology of the plasma cell dyscrasias (PCD), i.e., multiple myeloma, macroglobulinemia, amyloidosis, the heavy chain diseases and asymptomatic monoclonal gammopathies (Project I); 2) further characterize the monoclonal immunoglobulins associated with PCD's with respect to specific antibody activities (e.g., binding of haptens such as riboflavin) and physiochemical properties which relate to specific pathophysiological manifestations in individual cases, e.g., amyloidosis, hyperviscosity, disturbances of lipid metabolism, coagulation defects and renal dysfunction (Project II); 3) screen monclonal immunoglobulins for anticarbohydrate activity with the goal of identifying specific proteins for detailed analysis of primary, secondary and tertiary structure (Project III); 4) define the nature of cellular abnormalities in the plasma cell dyscrasias, i.e., the possible involvement of T as well as B cells and plasma cells, the distribution patterns of specific markers including idiotypic determinants and their potential use as targets for specific cytotoxicity (Project IV); and 5) investigate the specific interactions between the apparently neoplastic clones in the PCD's and the remaining immune system considered as a network of mutually regulating clones (Project V).